MEDI 9331 Scholarly Activities Clinical Years
Document Type
Article
Publication Date
Winter 2-28-2025
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In the United States alone, there are an estimated 42,000 adults being diagnosed with primary liver cancer within 2022. Sorafenib is the first systemic therapy approved for patients with advanced-stage HCC, after a landmark study revealed an improvement in the median overall survival of patients within 8 to 11 months. New drugs such as lenvatinib, serve as a frontline medication while other drugs such as regorafenib, cabozantinib, and ramucirumab, serve as second line medications. These drugs have been demonstrated to improve clinical outcomes; however, the median overall survival remains ~1 year. Therefore, the discovery of new potential molecular targets is required which could be used in rationale designing of the prevention and treatment strategies against advanced liver cancer. The ribosome biogenesis process is dysregulated in most cancer cells because of the high demand of protein synthesis. However, the role of ribosome biogenesis components was the least studied in cancer settings. Here, we found that POLR1A (RPA194), a catalytic subunit of RNA polymerase I, is significantly overexpressed (P<0.0001) in liver cancer tissues compared to normal tissues. It is interesting to note that fibrolamellar and hepatocellular carcinoma tissues from African Americans expressed this gene more than those from Caucasians and Asian Americans. POLR1A was surprisingly considerably overexpressed in mutant p53 liver cancer patients when compared to liver tumors harboring non-mutant p53, suggesting that mutant p53 is involved in controlling POLR1A. We also observed that mutant p53 bearing cancer cells have higher expression of POLR1A. Next, we evaluated the anti-cancer efficacy of specific pharmacological inhibitors of RPA194 by using an in vitro model system. We observed that targeting RPA194 induces apoptosis and suppresses the growth of several human liver cancer cell lines. Overall, these results suggest that RPA194 could be a novel potential molecular target and prognostic biomarker for mutant p53 liver cancer. Targeting RPA194 may be a successful treatment strategy for the management of patients with advanced liver cancer.
Recommended Citation
Bangash, Muhammad Ali; Bangash, Aun Ali; Ahsan, Haider; Rincon, Alejandro; and Hafeez, Bilal, "Clinical Significance of Targeting RNA Polymerase I in Hepatocellular Carcinoma" (2025). MEDI 9331 Scholarly Activities Clinical Years. 89.
https://scholarworks.utrgv.edu/som9331/89
Academic Level
medical student
Mentor/PI Department
Immunology and Microbiology
Included in
Amino Acids, Peptides, and Proteins Commons, Biological Factors Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Digestive System Diseases Commons, Disease Modeling Commons, Enzymes and Coenzymes Commons, Gastroenterology Commons, Genetic Processes Commons, Genetic Structures Commons, Hepatology Commons, Immune System Diseases Commons, Investigative Techniques Commons, Medical Biomathematics and Biometrics Commons, Medical Cell Biology Commons, Medical Genetics Commons, Medical Immunology Commons, Medical Molecular Biology Commons, Neoplasms Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Nutritional and Metabolic Diseases Commons, Oncology Commons, Other Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Therapeutics Commons
